Project abstract for group wilmotc

Synthesis of Unusual Enzyme Cofactors

The goal of this project is to understand the synthesis and function of novel organic, organometallic,and metal ion cofactors in proteins. The principal tool of the research is macromolecular x-ray crystallography. The project involves freeze-trapping reaction intermediates in the crystal to yield molecular “snapshots” along the reaction pathways through interrogation by x-rays. These can be assembled into “movies of catalysis” at the molecular level. By understanding these reactions in such detail, it is hoped that better drugs can be designed, proteins can be rationally engineered for biotechnological purposes, and chemists can design simpler industrial catalysts to control analogous reactions. Specific topics of interest to the Wilmot lab include structural enzymology involving hemes (chlorite dismutase, MauG, hydroxylamine oxidoreductase), assembly of the cofactor tryptophan tryptophylquinone of methylamine dehydrogenase, and molecular oxygen activation by the copper-containing amine oxidase from yeast.